title: High MMP-9 activity levels in fragile X syndrome are lowered by minocycline.
abstract: Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by lack of the FMR1 protein, FMRP, a translational repressor. Its absence leads to up-regulation of locally translated proteins involved in synaptic transmission and plasticity, including the matrix metalloproteinase-9 (MMP-9). In the Fmr1 knock-out (KO), a mouse model of FXS, an abnormal elevated expression of MMP-9 in the brain was pharmacologically down-regulated after treatment with the tetracycline derivative minocycline. Moreover, the rescue of immature dendritic spine morphology and a significant improvement of abnormal behavior were associated with down-regulation of MMP-9. Here, we report on high plasma activity of MMP-9 in individuals with FXS. In addition, we investigate MMP-9 changes in patients with FXS who have gone through a minocycline controlled clinical trial and correlate MMP-9 activity to clinical observations. The results of this study suggest that, in humans, activity levels of MMP-9 are lowered by minocycline and that, in some cases, changes in MMP-9 activity are positively associated with improvement based on clinical measures.
authors.affiliation: Nencki Institute, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dziembowska
authors.forename: Dalyir I
authors.initials: DI
authors.lastname: Pretto
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Janusz
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.forename: Mary Jacena
authors.initials: MJ
authors.lastname: Leigh
authors.forename: Nielsen
authors.initials: N
authors.lastname: Gabriel
authors.forename: Blythe
authors.initials: B
authors.lastname: Durbin-Johnson
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
mesh_terms: D000293:Adolescent; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000097:blood*; D005600:Fragile X Syndrome / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D051379:Mice; D008911:Minocycline / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D051860:Fragile X Messenger Ribonucleoprotein 1; D020780:Matrix Metalloproteinase 9; D008911:Minocycline
keywords: FXS; MMP-9; metalloproteinases; minocycline